avelumab in patients with previously treated advanced stage classical hodgkin's lymphoma (javelin hodgkins)

Conditions: Hodgkins Lymphoma

Summary: this is a phase 1b, open-label, multi-center study comprising a lead-in phase and an expansion phase. the lead-in phase is a multiple-dose, randomized, parallel-arm, pharmacokinetic and pharmacodynamic study of avelumab as a single agent in adult patients with chl. patients enrolled in the lead-in phase of this study are required to have relapsed following a prior autologous or allogeneic hsct, or to be ineligible for hsct. based on the preliminary to, safety, and efficacy results from the lead-in phase, the expansion phase will evaluate the anti-tumor activity and safety of single-agent avelumab utilizing an intra-patient dose escalation paradigm based on two of the dosing regimens studied in the lead-in phase in 40 chl patients in whom an allogeneic hsct has failed.


Eligibility criteria:
key inclusion criteria * histological confirmation of classical hodgkin's lymphoma (chl) with relapsed or refractory disease who, for the lead-in phase, either have had a prior autologous or allogeneic hsct or are not eligible for hsct, and , for the expansion phase, have had a prior allogeneic hsct. in the expansion phase there must be a documented cd3+ donor chimerism of ≥20%. * patients must be off previous chl therapy for at least 28 days prior to randomization in the lead-in phase/first dose of study treatment in the expansion phase. * at least 1 fluorodeoxyglucose (fdg) pet avid (deauville 4/5) measurable lesion \>1.5 cm on pet-ct scan as defined by the response criteria for malignant lymphoma (for the lead-in phase) and the lugano classification (for the expansion phase) that has not previously been irradiated. * expansion phase: required "de novo" or "archival" tumor biopsy, as well as required on treatment biopsy * estern cooperative oncology group (ecog) performance status 0 or 1 key exclusion criteria * patients with prior allogeneic hematopoietic stem cell transplantation (allo-hsct) who have had: 1. lead-in phase: allo hsct performed \ 4 months prior to the first dose of study treatment must have discontinued all immunosuppressive therapy, and must have no clinical evidence of gvhd; or 2. immunosuppressive treatment for acute or chronic gvhd within 3 months prior to randomization for the lead-in phase or prior to the first dose of study treatment for the expansion phase (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to first dose of study treatment; or 3. acute grade 3 or grade 4 gvhd at any time in the past (as defined by the modified seattle glucksberg criteria (consensus conference on acute gvhd grading criteria); or 4. prior chronic gvhd (as defined by the nih consensus development project) that persisted for \>6 months and required systemic immunosuppression (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to the first dose of study treatment; or 5. a donor lymphocyte infusion (dli) within 3 months prior to randomization for the lead-in phase or first dose of study treatment for the expansion phase. * prior therapy with an anti pd 1 or anti pd l1 mab. 1. lead-in phase: may be enrolled if patient stopped prior anti pd1 or anti-pd-l1 therapy more than one year prior to randomization and had a documented prior response. 2. expansion phase: prior therapy with an anti-pd-1 or anti-pd-l1 agent following allo-hsct is prohibited unless the therapy was stopped more than one year prior to the first dose of study treatment, and the patient had a documented prior response. note: prior therapy with an anti-pd-1 or anti-pd-l1 agent prior to allo-hsct is permitted with no time limits and irrespective of a documented response. 3. patients with a history of ≥grade 3 anti-pd-1 or anti-pd-l1-related immune toxicity are not eligible.

Keywords: classical hodgkins lymphoma (relapsed/refractory) post-allogeneic hsct anti pd-l1 phase 1 pk receptor occupancy immunophenotypic biomarkers